In this specification where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge; or known to be relevant to an attempt to solve any problem with which this specification is concerned.
Increasing Lean Body Mass
There are a number of diseases which involve cachexia (weakness and wasting of the body) as a symptom in which the body loses significant amounts of lean body mass. Examples of such diseases include diabetes, cancer, Alzheimers, bulimia nervosa and anorexia.
There is thus a need for a treatment which enables the body to increase its percentage of lean body mass with a minimal increase, or ideally a decrease, in the percentage of fat mass.
Polyphenols
Polyphenols (compounds with two or more phenolic hydroxy groups) are a class of phytochemicals found in a variety of sources including wine, grapes, cocoa and sugar cane. Polyphenols (or phenolics) all have a common basic chemical component, that is, a phenolic ring structure. There are at least 8000 identified polyphenols in a number of subcategories, such as anthocyanins and catechins. Natural polyphenols can range from simple molecules such as phenolic acid to large highly polymerized compounds such as tannins. Conjugated forms of polyphenols are the most common, where various sugar molecules, organic acids and lipids (fats) are linked with the phenolic ring structure. Differences in this conjugated chemical structure account for different chemical classifications and variation in the modes of action and health properties of the various compounds.
Polyphenols are considered to have a number of health benefits including:                antioxidant activity;        cancer preventative properties;        heart disease and hypertension protection;        antibiotic/antiviral activity;        anti-inflammatory activity;        ophthamological properties; and        protecting and strengthening blood vessels.        
Polyphenols are responsible for the brightly colored pigments of many fruits, vegetables and flowers (ranging from pink through scarlet, purple and blue), they protect plants from diseases and ultraviolet light and help prevent damage to seeds until they germinate.
Unfortunately, although the epidemiologic data for regular fruit and vegetable intake and disease prevention is strong, dietary supplements containing isolated phenolic antioxidants have not been extensively studied in terms of disease prevention. Products such as green tea, HCA (hyroxycitric acid) and inulin claim weight loss benefits based on the assumption that these products delay glucose absorption and/or regulate insulin to control appetite. This has yet to be proven in controlled clinical trials with humans (Functional Food Update 01, National Centre of Excellence in Functional Foods, Australia. June 2006).
Sugar Cane
Anthocyanins are polyphenolic flavylium salts with sugar units attached to the molecule and are derived chiefly from six anthocyanidins: pelargonidin, cyanidin, delphinidin, peonidin, petunidin and malvidin. These compounds differ in the position and number of hydroxyl groups in ring B but all have a sugar unit at the 3 position and are water soluble. With the exception of the petunidin group, representatives of all other anthocyanin classes have been located in sugar cane.
The basic structure common to all anthocyanins is as follows:
Tea
Second only to water, tea is one of the most widely consumed beverages in the world. Approximately 3.0 million metric tons of dried tea is produced annually, 20% of which is green tea, 2% is oolong and the remainder is black tea (International tea committee Annual bulletin of statistics 2002). Black, oolong and green tea are produced from the leaves of the tea plant Camellia sinensis, a member of the Theaceae family. Different varieties of tea are produced by varying the degree of leaf oxidation. Green tea is produced by steaming freshly harvested leaves at high temperatures, inactivating oxidative enzymes. This preserves the high polyphenol content found in green tea. Black tea leaves are the most oxidated, while oxidation of oolong tea leaves is midway between green tea and black tea.
The majority of polyphenols in tea are flavonols, specifically catechins. These small molecules react with one another during the oxidation process that produces black and oolong teas to form larger, highly colorful compounds called theaflavins and thearubigins.
There has recently been a lot of research into potential pharmaceutical benefits of the polyphenols extracted from tea. The most potent chemopreventive agent commonly extracted from tea is (−)-epigallocatechin-3-gallate (EGCG). There are also claims that green tea polyphenols can assist with weight loss because of its ability to increase metabolism and fat burning noted whilst studying the effect of polyphenols on cholesterol levels in the blood. Medicines made from tea polyphenols have become part of the treatment for nephritis, chronic hepatitis, and leukemia in China. In other countries, green tea supplements are available.
The basic structure common to all catechins is as follows:
Cocoa
Theobroma cocoa is a rich source of flavonoids including polyphenols. One study on the consumption of dark chocolate by humans has shown that flavonoid rich chocolate improves endothelial function and increases plasma epicatechin concentrations. However, that study found no change in oxidative stress measures, lipid profiles, blood pressure, body weight or body mass index [Engler et al, “Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults” J Am Coll Nutr 2004; 23(3):197-204].
Another study on the consumption of dark chocolate found no changes in the total antioxidant capacity of plasma or in the oxidation susceptibility of serum lipids. The study did find that cocoa polyphenols may increase the concentration of HDL cholesterol whereas chocolate fatty acids may modify the fatty acid composition of LDL and make it more resistant to oxidative damage [Mursu et al “Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans” Free Radic Biol Med 2004 Nov. 1; 37(9): 1351-9].
ACE Inhibitors
ACE is an important part of the renin-angiotensin-aldosterone system, one of the major endocrine systems in the body. ACE cleaves angiotensin I (ANG-I) to the potent vasoconstrictor angiotensin II (ANG-II) which regulates major physiological functions of the body including blood pressure, body sodium and fluid homeostasis which mediates its function via cellular receptors AT-1 and AT-2. ACE inhibitors have been demonstrated to be useful in lowering blood pressure and in the treatment of left ventricular dysfunction and diabetic neuropathy.
There have been a number of studies into the various roles of ANG-II:                organogenesis (Oliverio M I, Madsen K, Best C F, Ito M, Maeda N, Smithies O, Coffman T M. “Renal growth and development in mice lacking AT1A receptors for angiotensin II”. Am. J. Physiol. 1998; 274:F43-F50);        formation of pre-adipocytes;        human preadipocytes express a high affinity for AT-1 receptor substypes (Crandall D L, Armellino D C, Busier D E, McHendry-Rinde B, Kral J G. “Angiotensin II receptors in human preadipocytes: role in cell cycle regulation”. Endocrinology 1999; 140:154-158);        white adipose tissue has been reported to be an important site of angiotensinogen production (Cassis L A, Saye J, Peach M J. “Location and development of rat angiotensin messenger RNA”. 1988; Hypertension 11:591-596);        stimulate adipogenesis or formation of adipose (fat) cells (Darimont C, Vassaux G, Alihaud G, Negrel R. “Differentiation of preadipose cells: paracrine role of prostacyclin upon stimulation of adipose cells by angiotensin-II”. Endocrinology 1994; 135:2030-2036; Saint-Marc P. Kozak L P, Ailhaud G, Darimont C, Negrel R. “Angiotensin-II as a trophic factor of white adipose tissue: stimulation of adipose cell formation”. Endocrinology 2001; 142:487-492);        increase lipogenesis and triglyceride accumulation in preadipose cells and human adipocytes (Jones B H, Standridge M K, Moustaid N. “Angiotensin-II increases lipogenesis in 3T3-L1 and human adipose cells”. Endocrinology 1997; 138:1512-1519);        rats treated with an ACE inhibitor (losartan) exhibit a reduction in adipocyte size (Zorad S, Fickova M, Zelezna B, Macho L, Kral J G. “The role of angiotensin-II and its receptors in regulation of adipose tissue metabolism and cellularity”. Gen. Physiol. Biophys. 1995; 14:383-391)        
Collectively, these studies indicate that ANG-II plays an important role in the development of adipose tissue.
Studies have also shown that ACE inhibitors may be useful in reducing weight gain.                In angiotensinogen deficient mice, weight gain is lower than in normal wild type mice despite food intake being similar for both genotypes (Massiera F, Seydoux J, Geloen A, Quignard_Boulange A, Turban S, Saint-Marc P, Fukamizu A, Negrel R, Ailhaud G. and Teboul M. “Angiotensinogen-Deficient mice exhibit impairment of diet-induced weight gain with alteration in adipose tissue development and increase in locomotor activity”. Endocrinology 2001; 142(12):5220-5225).        Overfeeding of rodents leads to increased production of ANG-II and chronic ANG-II infusion results in a dose dependant reduction in body weight (Cassis L A, Marshall D E, Fettinger M J, Rosenbluth B, Lodder R A. “Mechanisms contributing to angiotensin II regulation of body weight”. Am. J. Physiol. Endocrinol. Metab. 1998; 274:E867-E876).        In obese human hypertensive patients, ANG-IT increases in adipocytes and may be a contributing factor in the development of insulin resistance. This may be aggravated by the inhibition of preadipocyte recruitment, which results in redistribution of fat to the liver and skeletal muscle. For this reason, ACE-inhibition may have potential in slowing the development of type 2 diabetes and pathophysiological roles of the adipose-tissue renin-angiotensin-receptor system in metabolic syndrome (Engeli S, Schling P, Gorzelniak K, Boschmann M, Janke J, Ailhaud G, Teboul M, Massiera F, Sharma A M. “The adipose-tissue renin-angiotensin-aldosterone system: role in metabolic syndrome”. The International Journal of Biochemistry & Cell Biology 2003; 35:807-825.)        
However, none of these studies disclose a method for changing body mass composition, eg, a reduced fat mass and increased lean muscle mass. Increasing lean body mass is not necessarily associated with a weight loss. There is thus still a need for such a method to assist subjects suffering from cachexia.
Dairy Bioactives, Leucine, Ace Inhibitory Peptides and Other Branched Chain Amino Acids
Milk bioactives, leucine and other branched chain amino acids are natural angiotensin converting enzyme (ACE) inhibitors. ACE inhibitory peptides may be released by proteolysis of milk proteins by lactic acid bacterial during cheese ripening. They may also be isolated from milk and whey during fermentation (Fitzgerald R J, Murray B A. “Bioactive Peptides and lactic fermentations”. International Journal of Dairy Technology 2006; 59(2):118-125). ACE inhibitory dairy peptides have an IC50 values >520 μm and sufficient amounts may be delivered via fermented milks and extracts of fermented dairy products. Although weight reduction has been proposed using dairy products (Zemel M B et al. “Dairy augmentation of total and central fat loss in obese subjects”. Int. J. Obes. Belot. Metab. Disord. 2005; 29(4):391-7), the role in weight management has recently been questioned (Gunther C W et al. “Dairy products do not lead to alterations in body weight or fat mass in young women in a 1-y intervention”. Am. J. Clin. Nurt. 2005; 81:751-756).
Obesity
A method for increasing the proportion of lean body mass could also be useful for treating subjects suffering obesity.
Every person has and needs fat tissue in their body. When there is too much body fat, the result is obesity. There are over 300 million obese adults, according to the World Health Organization and 1.1 billion overweight people worldwide.
The number of overweight and obese Americans has continued to increase since 1960, a trend that is not slowing down. More than half of US adults are overweight (64.5 percent) and nearly one-third (30.5 percent) are obese. Each year, obesity causes at least 300,000 excess deaths in the US, the and healthcare costs of American adults with obesity amount to approximately $100 billion. It is the second leading cause of preventable death after smoking.
Obesity increases one's risk of developing conditions such as high blood pressure, diabetes (type 2), heart disease, stroke, gallbladder disease and cancer of the breast, prostate and colon. The tendency toward obesity is fostered by our environment: lack of physical activity combined with high-calorie, low-cost foods. If maintained, even weight losses as small as 10 percent of body weight can improve one's health.
Being obese and being overweight are not the same condition. Your bathroom scale may give you a measure of your weight and help you follow changes in your weight, but it is not the best way to determine if you are overweight or obese, or at risk for developing obesity and its related health conditions.
In order to determine whether a person is obese, both body mass index (BMI) and waist circumference is needed. You can have a BMI that indicates you have a healthy weight, but still have a waist measurement above the healthy range.                BMI: is a number based on both height and weight. It can help to determine the degree to which a person may be overweight and gives a reasonable assessment of total body fat for the general population. BMI correlates better with health conditions like heart disease and type 2 diabetes than does weight itself. BMI is not perfect. Some people, like athletes, may measure a high BMI but have more muscle than fat. BMI “cutpoints” are numbers used to help you determine if you are at a healthy weight, overweight, obese or severely obese. It is important to note that BMI is different to Health/Weight tables.                    18.5 to 24.9=Healthy Weight            25 to 29.9=Over-weight            30 to 34.9=Obesity (class 1)            35 to 39.9=Obesity (class 2)            40 or more=Severe Obesity (class 3)                        Waist circumference measurement is used to determine health risks related specifically to abdominal fat.                    For Men: 40 inches or more            For Women: 35 inches or more                        
If your waist measurement is more than that listed above, and your BMI is between 25 and 34.9, you have an increased risk of developing type 2 diabetes, hypertension and cardiovascular disease.
Causes of Obesity
There are many factors that contribute to causing obesity including genetics, the environment and behaviour.                Genes: Some individuals have a genetic tendency to gain weight and store fat. Although not everyone with this tendency will become obese, some persons without genetic predisposition do become obese. Several genes have been identified as contributors to obesity, and researchers are constructing a Human Obesity Gene Map to identify genetic targets in humans that may lead to the development of new treatments.        Environment: An environment that promotes healthy weight is one that encourages consumption of nutritious foods in reasonable portions and regular physical activity. A healthy environment is important for all individuals to prevent and treat obesity and maintain weight loss. Identifying and consciously avoiding high-risk situations in the environment can assist in weight control efforts.        Behaviour: Adopting healthy habits for lifelong weight control include regular physical activity and nutritious eating. Specific behavioural strategies for weight loss and maintenance include: logging and tracking diet and exercise patterns in a diary, eating a low calorie diet, limiting the amount of calories from fat, expending calories routinely through exercise, monitoring weight regularly, setting realistic goals, and developing a social support network.        
The number of obese people in the world is increasing despite the above knowledge. There is thus a need for methods to modify body mass distribution.